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1,25-Dihydroxyvitamin D₃ Receptor Distribution and Effects in Subpopulations of Normal Human T Lymphocytes^*

Section of Endocrinology and Metabolism, Veterans Administration Medical Center, and the Department of Medicine, Indiana University (S.C.M.) Indianapolis, Indiana 46202
The Department of Immunology, Scripps Clinic and Research Foundation (D.M.P.) La Jolla, California 92037

Address all correspondence and requests for reprints to: Stavros C. Manolagas, M.D., Ph.D., Veterans Administration Medical Center (111E), 1481 West 10th Street, Indianapolis, Indiana 46202.

Receptors for l,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] are expressed upon activation of human lymphocytes, and the hormone inhibits in vitro the proliferation of mitogenactivated lymphocytes. In this study we examined the distribution of the 1,25-(OH)₂D₃ receptor protein in the two major subsets of T lymphocytes (T helper and T suppressor cells) and the effect of the hormone on their respective rates of proliferation. We activated normal lymphocytes in the presence of monocytes with phytohemagglutinin and subsequently isolated the T helper (T4-positive) and the T suppressor (T8-positive) subsets using monoclonal antibodies and complement-mediated lysis. In parallel experiments, we first isolated monocyte-depleted T4 and T8 cells and then activated them using phytohemagglutinin and a phorbol ester. Using either approach we found that both T4 and T8 lymphocytes expressed the 1,25-(OH)₂D₃ receptor protein upon activation. The concentration of this protein, its affinity for the ligand (K_d, 10^–10 mol/L), and its sedimentation characteristics (S = 3.3) were indistinguishable in the two T cell subsets. Furthermore, the time kinetics of expression of the receptor after activation were very similar in the two subsets. Nevertheless, 1,25-(OH)₂D₃ inhibited in a dose-dependent fashion the rate of proliferation of the helper subset, but had no effect on the proliferation of suppressor cells. The finding of a dissimilar effect of 1,25-(OH)₂D₃ on the proliferation of the T helper and T suppressor cells despite their indistinguishable receptor status suggests that the 1,25-(OH)₂D₃ receptors of the T cells might not be involved in the effects of the hormone on T-cell proliferation, and that the l,25-(OH)₂D₃-induced inhibition of mitogen-activated T4 cell proliferation could be mediated indirectly.

^* This work was supported by the NIH (AI-21761) and the V.A.

Received September 22, 1988.

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